Association of a transmembrane polymorphism of Fcgamma receptor IIb (FCGR2B) with systemic lupus erythematosus in Taiwanese patients

OBJECTIVE: To investigate the possible association of the Fcgamma receptor IIb (FcgammaRIIb) Ile/Thr187 transmembrane domain polymorphism, which significantly affects receptor signaling, with susceptibility to systemic lupus erythematosus (SLE) in Taiwanese patients. METHODS: We used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry to genotype 351 Taiwanese SLE patients and 372 age- and sex-matched healthy individuals from the same geographic area. Allele frequencies and genotype distributions were compared between the patients and controls, both as an aggregate and as stratified by sex, autoantibody profile, and clinical parameters. A combined analysis was conducted to assess the FCGR2B Thr187 allele as a common risk factor in different ethnic populations. RESULTS: The minor Thr187 allele was significantly associated with SLE in Taiwanese subjects (P = 0.017, odds ratio [OR] 1.989 [95% confidence interval (95% CI) 1.119-3.553]). Interestingly, male SLE patients showed enrichment of the Thr/Thr187 genotype (24%; 7 of 29) as compared with female SLE patients (10%; 32 of 322) (P = 0.043, OR 2.884 [95% CI 1.028-7.839]). Additionally, SLE patients with Thr/Thr187 and Ile/Thr187 genotypes were more likely to have pleural effusions (P = 0.038, OR 1.874 [95% CI 1.033-3.411]) and anti-SSA/Ro antibody production (P = 0.046, OR 2.221 [95% CI 1.013-4.897]). Combined analysis of 4 groups of Asian patients strongly supported the association of the FCGR2B Thr187 allele with the lupus phenotype (P = 0.000159). CONCLUSION: The FcgammaRIIb transmembrane polymorphism is a strong disease susceptibility candidate in epistasis with other genetic effects in Taiwanese and other Asian populations. It may also play a more prominent role in male patients with SLE.     

Association of apolipoprotein A1-C3 gene cluster polymorphisms with gallstone disease.

INTRODUCTION: Genetic polymorphisms in apolipoprotein genes may be associated with alteration in lipid profile and susceptibility to gallstone disease. AIM: To determine the association between apolipoprotein A1 (APOA1) -75 guanine [G] to adenine [A] and +83/84 M2(+/-), MspI) and apolipoprotein C3 (APOC3) (SstI) polymorphisms with gallstone disease. METHODS: MspI polymorphisms of the APOA1 gene and SstI polymorphisms of APOC3 were analyzed in DNA samples of 214 gallstone patients and 322 age- and sex-matched healthy controls. All statistical analyses were performed using SPSS version 11.5 (SPSS, USA) and Arlequin version 2.0 (Arlequin, Switzerland). RESULTS: The APOA1 -75 G/A polymorphism was significantly associated with gallstone disease. Patients with the GG genotype (P=0.015) and G allele carriers (P=0.004) had a significantly higher risk of gallstone disease (1.087-fold and 1.561-fold, respectively), whereas patients with AA genotypes (P=0.011) and A allele carriers (P=0.004) were protected (OR 0.230 and 0.641, respectively) against gallstone disease. APOA1 +83 M2(+/-) and APOC3 SstI polymorphisms were not associated with gallstone disease. Case-control analysis of haplotypes showed a significant association in males only. G-M2(+)-S1 conferred risk for gallstone disease (P=0.036; OR 1.593, 95% CI 1.029 to 2.464), while A-M2(+)-S1 was protective (P=0.002; OR 0.370, 95% CI 0.197 to 0.695) against gallstone disease. In APOA1(-75)-APOA1(+83) bilocus haplotypes, G-M2(+) was associated (P=0.0001) with very high risk (OR 3.173, 95% CI 1.774 to 5.674) for gallstone disease in males only. APOA1(-75)-APOC3(SstI) haplotypes also showed significant association while APOA1(+83)-APOC3(SstI) haplotypes showed no association with gallstone disease. CONCLUSIONS: The APOA1 -75 G/A polymorphism is associated with gallstone disease and shows sex-specific differences. On the other hand, APOA1 M2(+/-) and APOC3 SstI polymorphisms may not be associated with gallstone disease. Haplotype analysis is a better predictor of risk for gallstone disease.     

A prospective study of the APOA1 XmnI and APOC3 SstI polymorphisms in the APOA1/C3/A4 gene cluster and risk of incident myocardial infarction in men

BACKGROUND: Apolipoproteins AI/CIII/AIV play important roles in the metabolism of triglycerides (TG) and high-density lipoprotein (HDL) cholesterol. However, whether genetic variations in the APOA1/C3/A4 gene cluster are associated with the risk of myocardial infarction (MI) remains uncertain and prospective data are sparse. METHODS: In a prospective nested case-control study of 385 incident cases of MI and 373 age- and smoking-matched controls from the Physicians' Health Study, we examined the relationship between 2 common single nucleotide polymorphisms (APOA1 XmnI and APOC3 SstI) in the APOA1/C3/A4 gene cluster and haplotypes defined by these SNPs and risk of incident MI. RESULTS: No significant differences in allele or genotype frequency for the APOA1 XmnI and APOC3 SstI polymorphisms were detected between cases and controls. After adjusting for non-lipid coronary risk factors, the relative risks for incident MI were 1.00 (95% CI 0.68-1.47) for men carrying the X2 allele compared with those homozygous for the X1 allele in the APOA1 XmnI site and 1.07 (95% CI 0.69-1.64) for men carrying the S2 versus those homozygous for the S1 allele in the APOC3 SstI site. Moreover, we did not observe any effect modification by HDL or TG levels for the associations of these APOA1 and APOC3 genotypes with MI risk. There were significant differences in TG levels among men carrying different haplotypes (P=0.01) and men carrying the X1-S2 haplotype had higher levels of TG than those carrying the X2-S1 haplotype (202 mg/dl versus 157 mg/dl, P=0.03); however, haplotype frequencies defined by these two polymorphisms did not differ significantly between cases and controls. CONCLUSION: In this prospective study of apparently healthy middle-aged US men, carriers of the X1-S2 haplotype in the APOA1 XmnI and APOC3 SstI variants across the APOA1/C3/A4 gene cluster had higher TG levels, but there was no evidence for significant associations between these two common variants or haplotypes defined by them and risk of incident MI in this cohort.     

Association of a DNA polymorphism of the apolipoprotein AI-CIII-AIV gene cluster with myocardial infarction in a Tunisian population

Background

Apolipoproteins AI-CIII-AIV play important roles in the metabolism of triglycerides and high-density lipoprotein cholesterol. However, whether genetic variations in the ApoAI-CIII-AIV gene cluster are associated with the risk of myocardial infarction (MI) remains uncertain. In the present study, we examined a possible association of the ApoCIII SacI polymorphism in the ApoAI-CIII-AIV gene cluster with lipid parameters and MI in a sample of the Tunisian population.

Methods

A total of 326 Tunisian patients with MI and 361 controls were included in the study. Genotypes were determined by polymerase chain reaction — restriction fragment length polymorphism (PCR-RFLP) analysis.

Results

A significant difference in genotype distribution and allele frequency was observed between patients and controls. At the multivariate analysis after adjustment for traditional vascular risk factors, the ApoCIII SacI polymorphism was significantly associated with MI, according to co-dominant and dominant models (co-dominant model odds ratio [OR]: 1.53, 95% confidence interval [CI]: 1.0-2.35, p = 0.04; dominant model OR: 2.02, 95% CI: 1.11-3.67, p = 0.02). The MI patient group showed a significant higher frequency of the S2 allele compared to the controls (10.2% vs. 6.5%; OR: 1.64, 95% CI: 1.10-2.47, p = 0.01). There was no statistically significant association between ApoAI-CIII-AIV cluster gene polymorphism and lipid, lipoprotein, and apolipoprotein levels in both MI patients and controls.

Conclusion

In the current study, a significant association between the ApoCIII SacI polymorphism (presence of S2 allele) and MI in the Tunisian population was found.     

The -1131T>C polymorphism in the apolipoprotein A5 gene is related to hypertriglyceridemia in Taiwanese aborigines

The prevalence of hypertriglyceridemia, considered to be an independent risk factor for the development of cardiovascular disease, is high in Taiwanese aborigines. This study was undertaken to examine the effect of the -1131T>C polymorphism in the apolipoprotein A5 gene on serum triglyceride levels in female Taiwanese aborigines. This was a cross-sectional study, and a total of 316 unrelated female Taiwanese aborigines were genotyped at the -1131T>C polymorphism in apolipoprotein A5 using the polymerase chain reaction-restriction fragment length polymorphism method. Serum triglyceride > or = 150 mg/dL was defined as the hypertriglyceridemia group and triglyceride < 150 mg/dL was considered to be the control group. The frequency of the minor C allele was significantly higher in the hypertriglyceridemia group (0.53) than in the control group (0.35) (p < 0.001). The frequency of this rare allele was comparable to that in Japanese and Han Chinese, but was higher than that in Caucasians. In a multiple logistic model adjusted for possible confounders, C allele-containing variants were independently associated with greater risks (CT genotype: OR = 3.28, 95% CI = 1.43-7.56; CC genotype: OR = 5.86, 95% CI = 2.15-15.99) of hypertriglyceridemia than the TT genotype (p < 0.01), notably with the CC homozygote exhibiting the greatest risks. The genotype polymorphisms were also associated with serum triglyceride concentrations in a linear fashion (for trend, p < 0.05). Our results indicate that the -1131T>C polymorphism of the Apo A5 gene influences serum triglyceride levels in female Taiwanese aborigines, and that differences exist in the frequency of the C allele among people of various ethnicities.     

Impact of lipoprotein lipase gene polymorphisms on ulcerative colitis

INTRODUCTION Inflammatory bowel disease (IBD), characterized by chronic recurrent inflammation of the intestinal tract, includes two common forms: Crohn’s disease (CD) and ulcerative colitis (UC). For both forms, the etiology is unclear, but likely to be…     

Association of lipoprotein lipase gene polymorphisms with coronary artery disease

OBJECTIVES: The purpose of this study was to test whether the HindIII (+) and PvuII (-) or (+) restriction enzyme-defined alleles are associated with angiographic coronary artery disease (CAD). BACKGROUND: Lipoprotein lipase (LPL) plays a central role in lipid metabolism, hydrolyzing triglyceride in chylomicrons and very low density lipoproteins. Polymorphic variants of the LPL gene are common and might affect risk of CAD. METHODS: Blood was drawn from 725 patients undergoing coronary angiography. Leukocyte deoxyribonucleic acid segments containing the genomic sites were amplified by the polymerase chain reaction and digested, and polymorphisms were identified after electrophoresis in 1.5% agarose gel. RESULTS: In no-CAD control subjects (n = 168), HindIII (-) and (+) allelic frequencies were 28.6% and 71.4%, and (-) and (+) alleles were carried by 44.0% and 86.9% of subjects, respectively. Control PvuII (-) and (+) allelic frequencies were 41.7% and 58.3%, and (-) and (+) alleles were carried by 64.3% and 81.0%, respectively. In CAD patients (>60% stenosis; n = 483), HindIII (+) allelic carriage was increased (93.8% of patients, odds ratio [OR] = 2.28, confidence interval [CI] 1.27 to 4.00). Also, PvuII (-) allelic carriage tended to be more frequent in CAD patients (OR = 1.33, CI 0.92 to 1.93). Adjusted for six CAD risk factors and the other polymorphism, HindIII (+) carriage was associated with an OR = 2.86, CI 1.50 to 5.42, p = 0.0014, and PvulI (-) carriage, OR = 1.42, CI 0.95 to 2.12, p = 0.09. The two polymorphisms were in strong linkage disequilibrium, and a haplotype association was suggested. CONCLUSIONS: The common LPL polymorphic allele, HindIII (+), is moderately associated with CAD, and the PvuII (-) allele is modestly associated (trend). Genetic variants of LPL deserve further evaluation as risk factors for CAD.     

Association of a transmembrane polymorphism of Fcγ receptor IIb (FCGR2B) with systemic lupus erythematosus in Taiwanese patients

Objective

To investigate the possible association of the Fcγ receptor IIb (FcγRIIb) Ile/Thr187 transmembrane domain polymorphism, which significantly affects receptor signaling, with susceptibility to systemic lupus erythematosus (SLE) in Taiwanese patients.

Methods

We used matrix‐assisted laser desorption ionization−time‐of‐flight mass spectrometry to genotype 351 Taiwanese SLE patients and 372 age‐ and sex‐matched healthy individuals from the same geographic area. Allele frequencies and genotype distributions were compared between the patients and controls, both as an aggregate and as stratified by sex, autoantibody profile, and clinical parameters. A combined analysis was conducted to assess the FCGR2B Thr187 allele as a common risk factor in different ethnic populations.

Results

The minor Thr187 allele was significantly associated with SLE in Taiwanese subjects (P = 0.017, odds ratio [OR] 1.989 [95% confidence interval (95% CI) 1.119–3.553]). Interestingly, male SLE patients showed enrichment of the Thr/Thr187 genotype (24%; 7 of 29) as compared with female SLE patients (10%; 32 of 322) (P = 0.043, OR 2.884 [95% CI 1.028–7.839]). Additionally, SLE patients with Thr/Thr187 and Ile/Thr187 genotypes were more likely to have pleural effusions (P = 0.038, OR 1.874 [95% CI 1.033–3.411]) and anti‐SSA/Ro antibody production (P = 0.046, OR 2.221 [95% CI 1.013–4.897]). Combined analysis of 4 groups of Asian patients strongly supported the association of the FCGR2B Thr187 allele with the lupus phenotype (P = 0.000159).

Conclusion

The FcγRIIb transmembrane polymorphism is a strong disease susceptibility candidate in epistasis with other genetic effects in Taiwanese and other Asian populations. It may also play a more prominent role in male patients with SLE.

     

Polymorphisms of HER2 Ile655Val and cyclin D1 (CCND1) G870A are not associated with breast cancer risk but polymorphic allele of HER2 is associated with nodal metastases

The HER2 codon Ile655Val and Cyclin D1 (CCND1) G870A polymorphisms were analyzed in a hospital-based Malaysian population using PCR-RFLP method. Peripheral blood samples were collected from 230 breast cancer patients, and 200 normal and healthy women who had no history of breast disease or breast cancer. We evaluated the association between HER2 or CCND1 polymorphisms and breast cancer risk, and clinico-pathological parameters in the population. The genotype and allele frequencies of HER2 (P=0.163 vs P=0.0622) and CCND1 (P=0.377 vs P=0.284) polymorphisms were not significantly different between the breast cancer cases and normal subjects, respectively. Women who were Ile/Val heterozygotes (OR=1.48; 95% CI, 0.91-2.43), Val/Val homozygotes (OR=1.93; 95% CI, 0.51-7.77) and carriers of Val allele genotype (OR=1.53; 95% CI, 0.95-2.45) were not significantly associated with increased breast cancer risk. Similarly, women who were homozygous (OR=1.34; 95% CI, 0.77-2.34) or heterozygous (OR=0.98; 95% CI, 0.60-1.60) for A allele, or carriers of A allele genotype (OR=1.10; 95% CI, 0.70-1.73) were not associated with breast cancer risk. Analysis on clinico-pathological parameters showed that Val allele genotype was significantly correlated with nodal metastases but A allele genotype was not associated with any of the variables. Our findings suggest that the polymorphic alleles of HER2 and CCND1 may not play an important role as genetic markers for breast cancer risk, but presence of Val allele may be useful for tumor prognosis.     

Association of single nucleotide polymorphism rs2076185 in chromosome 6P24.1 with premature coronary artery diseases in Chinese Han population

Objectives To study the association of single nucleotide polymorphism (SNP) rs2076185 in chromosome 6p24.1 with the premature coronary artery diseases (PCAD) in Chinese Han population. Methods A total of 1382 patients were divided into the PCAD group and the control group based on their coronary arteriography (CAG) results. Their SNP rs2076185 were analyzed by the mass-spectrometry. Their allele and genotype frequency in Hardy-Weinberg equilibrium were calculated for assessment. Logistic regression was employed to remove confounding factors and correlate SNP rs2076185 with PCAD. Results The allele and genotype frequencies of the control group were in Hardy-Weinberg equilibrium (P > 0.05). The frequencies of allele G of rs2076185 were 54.2% in the PCAD group and 49.5% in the control group. The difference was significant (P = 0.042). The genotype distribution of rs2076185 of the two groups was also significantly different. The univariate analysis showed that the rs2076185 polymorphisms were associated with the PCAD only in the additive model (OR: 0.828, 95% CI: 0.711?0.964, P = 0.014), and in the dominant model (OR: 0.753, 95% CI: 0.591?0.958, P = 0.021). After removing the confounding variables, the rs2076185 polymorphisms was associated with PCAD in the additive model (OR: 0.775, 95% CI: 0.648?0.928, P = 0.005), in the dominant model (OR: 0.698, 95% CI: 0.527?0.925, P = 0.012), and in the recessive model (OR: 0.804, 95% CI: 0.538?0.983, P = 0.038). Conclusion Allele G of rs2076185 reduces the PCAD risks in Chinese Han population, therefore it could be a coronary artery diseases protective factor in Chinese Han population.     

Gender specific associations of the Trp64Arg mutation in the beta3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation

OBJECTIVE: To investigate the association between the Trp64Arg beta3-adrenergic receptor (ADRB3) mutation and obesity-related phenotypes in a Mediterranean Spanish population considering the effect of other genetic and environmental factors. DESIGN AND SUBJECT: Cross-sectional study in 1063 (476 men and 587 women) randomly selected from this population (aged: 18-68 years). MEASUREMENTS: Anthropometric (weight, height and waist-to-hip ratio), blood pressure, biochemical (lipids, fasting glucose, and uric acid), life-style variables, and the Trp64Arg, HindIII-Lipoprotein lipase (LPL) and apolipoprotein E polymorphism. RESULTS: Frequency of the Arg64 allele was low (0.051; 95% CI: 0.042-0.060). We found gender-specific associations between the Trp64Arg mutation and obesity related phenotypes. In men, carriers of the Arg64 variant had higher body mass index (BMI) (27.63 +/- 3.81 vs. 26.34 +/- 3.57 kg m-2, P=0.049) and total cholesterol (5.85 +/- 1.45 vs. 5.28 +/- 1.06 mmol L-1; P=0.011) compared with wild-type individuals. Logistic regression analysis, revealed that the risk of overweight was two times higher in male carriers of the Arg64 allele. In women, the Arg64 variant was only associated with higher fasting glucose (P=0.031). These genotype effects persisted after adjustment for age, genetic and life-style variables. For the LPL polymorphism, the H-/H- genotype was associated with lower BMI and with lower risk of overweight (OR: 0.49; 95% CI: 0.30-0.81) in both men and women. However, after adjustment for covariates, these associations only remained statistically significant (P < 0.02) in women. Moreover, in women, a statistically significant interaction (P=0.026) between the LPL and the ADRB3 gene loci in determining BMI was found. Thus, the Arg64 allele was associated with a higher BMI only in H+/H+ women. CONCLUSIONS: The Trp64Arg mutation was associated with BMI and lipids in men. In women, an additional gene-gene interaction with the LPL-HindIII polymorphism may explain the results.     

beta1- and beta2-adrenergic receptor gene variation, beta-blocker use and risk of myocardial infarction and stroke

BACKGROUND: The benefits of beta-blocker therapy may depend on underlying genetic susceptibility. METHODS: We investigated the interaction of common variation in beta1 and beta2 adrenergic receptor (AR) genes with beta-blocker use on the risks of myocardial infarction (MI) and ischemic stroke in a case-control study. Participants were treated pharmacologically for hypertension, aged 30-79 years, with incident MI (n = 659) or ischemic stroke (n = 279) between 1995 and 2004, and 2,249 matched controls. RESULTS: We observed an interaction of beta-blocker use with beta1-AR gene variation on MI risk (P value, 6 degrees of freedom: 0.01) and ischemic stroke risk (P value, 6 degrees of freedom: 0.04). Compared with use of other antihypertensive medications, beta-blocker use was associated with higher MI risk in carriers of one or two copies of rs#17875422 (Odds ratio (OR): 2.66, 95% confidence interval (CI); 1.26-5.60) but not in homozygous carriers of the common allele (OR: 0.88, 95% CI: 0.73-1.07). Another variant, rs#2429511, interacted with beta-blocker use on both MI and ischemic stroke risks. beta-blocker use was associated with higher risk of combined MI and ischemic stroke in carriers of rs#2429511 (OR: 1.24, 95% CI: 1.03-1.50) but not in homozygous carriers of common allele (OR: 0.70, 95% CI: 0.51-0.94). beta-blocker use did not interact with beta2-AR gene variation on the risks of MI and ischemic stroke. CONCLUSIONS: These results, which require replication, suggest genetic variants in the beta1-AR gene may determine whether to use beta-blockers in hypertension for the primary prevention of cardiovascular disease.     

A/C polymorphism in the interleukin-18 coding region among Taiwanese systemic lupus erythematosus patients

Interleukin-18 (IL-18) is associated with chronic inflammation, autoimmune diseases and various cancers and infectious diseases. An IL-18 genetic A/C polymorphism at coding position 105 (rs549908) has been linked with asthma and rheumatoid arthritis. We tested a hypothesis that the IL-18 genetic polymorphism confers systemic lupus erythematosus (SLE) susceptibility. Study participants were Taiwanese SLE patients and a healthy control group. Our results indicate (1) a significantly higher A allele frequency in SLE patients (P = 0.003; OR = 1.97; 95% CI = 1.26-3.08) and (2) a significantly higher A allele frequency in SLE patients with a central nervous system disorder (P = 0.027; OR = 7.18; 95% CI = 0.95-54.28). Our results suggest that the A/C polymorphism contributes to SLE pathogenesis.     

Sonographic fatty liver and hepatitis B virus carrier status： Synergistic effect on liver damage in Taiwanese adults

AIM: To examine the epidemiology of hepatitis B virus carrier status (HBVC) and sonographic fatty liver (SFL) in Taiwanese adults, and to evaluate their possible interaction in inducing liver damage (LD). From an epidemiological viewpoint, we analyzed previous studies which indicated that fatty liver sensitizes host immune response to HBV infection and enhances liver damage.METHODS: A cross-sectional retrospective analysis of health records including medical history, physical examination, abdominal sonogram, blood biochemistry and hepatic virological tests. We utilized the Student's t-test, chi-square, multivariate logistic regression and synergy index to assess risks for LD.RESULTS: Among a total of 5406 Taiwanese adults (mean age 46.2 years, 51.5% males), the prevalence of LD, HBVC and SFL were 12.3%, 15.1% and 33.4%, respectively; 5.1% of participants had SFL plus HBVC. Multivariate logistic regression analysis demonstrated that male gender (odds ratio (OR) = 2.8, 95% confidence interval (CI): 2.3-3.5), overweight state (OR = 1.6, 95% CI: 1.3-2.0), HBVC (OR = 2.5, 95% CI: 2.0-3.1) and SFL (OR = 4.2, 95% CI: 2.2-5.3) were independently associated with LD. Synergism analysis showed that the adjusted OR for LD in adults with HBVC-alone was 3.3 (95% CI: 2.4-4.6), SFL-alone, 4.7 (95% CI: 3.7-6.1) and combined HBVC and SFL, 9.5 (95% CI: 6.8-13.3); the synergy index was 1.4 (95% CI: 1.001-2.0).CONCLUSION: In Taiwanese adults, SFL plus HBVC have a significant synergistic association with LD.     

Inhibition of Akt phosphorylation by thrombin,histamine and lysophosphatidylcholine in endothelial cells. Differential role of protein kinase C

This randomised, double-blind, placebo-controlled crossover study evaluated the effects of rosuvastatin (40 mg/day for 8 weeks) on atherogenic apolipoprotein B-containing lipoprotein subfractions. Subjects, recruited based on raised plasma triglyceride (TG) or low-density lipoprotein cholesterol (LDL-C), were divided into normotriglyceridaemic (NTG, n = 13; TG < 2.0 mmol/l) and hypertriglyceridaemic (HTG, n = 16; TG > or = 2.0 mmol/l) groups. Similar reductions on rosuvastatin were observed for both groups in LDL-C (NTG -60%; HTG -56%), apoB (both -49%), intermediate-density lipoprotein (NTG -57%; HTG -54%) and LDL circulating mass (NTG -52%, HTG -58%) (all P < 0.001 versus placebo), i.e., these changes were phenotype independent. Phenotype dependency in response was observed in HTG relative to NTG in concentration of small dense LDL (LDL-III) (NTG -44%, P = NS; HTG -69%, P < 0.001), very-low-density lipoprotein1 (NTG -18%, P = NS; HTG 46%, P < 0.01), and remnant-like particle cholesterol (NTG -31%, P = NS; HTG -48%, P < 0.05). Rosuvastatin reduced cholesteryl ester transfer protein (CETP) by 33% in NTG and 37% in HTG (both P < 0.001); a reduction in cholesteryl ester transfer activity (-59%, P < 0.001) was observed in HTG only. Rosuvastatin therefore, in addition to lowering LDL and apoB-concentrations, largely corrected the TG and LDL abnormalities in subjects who had the propensity to develop the atherogenic lipoprotein phenotype.     

Factors associated with the presence of multiple Lugol‐voiding lesions in patients with esophageal squamous‐cell carcinoma

Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol‐voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence‐specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84–122.45: P = 0.011), presence of the ALDH2‐2 allele (OR 4.5, 95% CI 1.55–13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02–6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13–88.44: P = 0.038) and presence of the ALDH2‐2 allele (OR 4.56, 95% CI 1.4–14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2‐2 allele (OR 17.5, 95% CI 1.97–155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2‐2 allele (OR 8.85, 95% CI 1.68–46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2‐2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2‐2 allele (OR 4.0, 95% CI 0.54–29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2‐2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2‐2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.     

Influence of HLA-DRB1 genes and the shared epitope on genetic susceptibility to rheumatoid arthritis in Taiwanese

OBJECTIVE:To investigate the association of predisposing and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in a Taiwanese population. METHODS: A total of 273 patients with RA and 480 healthy controls, all of Taiwanese origin, were genotyped for HLA-DRB1 alleles by polymerase chain reaction and sequence-based typing assays. The associations between RA and HLA-DRB1 alleles and genotypes were investigated by chi-squared test. RESULTS: The DRB1*0405 and *1001 phenotypes showed the most significant associations with RA (OR 4.04, 95% CI 2.84-5.77, pc = 3.2 10(-14); OR 5.25, 95% CI 2.10-13.06, pc = 3.0 10(-3), respectively). Individuals carrying single or double doses of the shared epitope (SE/non-SE or SE/SE) had higher risks of RA. The compound heterozygote of DRB1*0405/*1001 showed the largest increase in RA risk (OR 15.8, 95% CI 2.48-100.7, pc = 0.004). Single or double doses of SE alleles were significantly associated with a higher bone erosion rate. Rheumatoid factor positivity and bone erosion were more frequent in patients with at least one copy of DRB1*0405. CONCLUSION: Our results show that SE-encoding HLA-DRB1*0405 and *1001 are associated with RA in a Taiwanese population; this is the first time DRB1*1001 has been described in persons of Asian ethnicity. Heterozygotes of DRB1*0405 and *1001 predicted the strongest susceptibility to RA, suggesting that this genotype enhances susceptibility to RA in Taiwanese.     

Angiotensin-converting enzyme gene polymorphism in north Indian population with obstructive sleep apnea

Background

A deletion of 287-bp Alu repeat of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene is associated with hypertension.

Purpose

The aim of this study is to determine the frequency of ACE (I/D) polymorphism in patients with obstructive sleep apnea (OSA).

Methods

Genotyping of ACE (I/D) gene polymorphism and estimation of serum angiotensin-converting enzyme (SACE) activity were done in 813 subjects who underwent polysomnography. Of these, 395 were apneics and 418 were non-apneics.

Results

The frequencies of II genotype (OR = 1.8, 95 % CI 1.26–2.60, p?=?0.001) and I allele (OR = 1.4, 95 % CI 1.13–1.69, p?=?0.001) of ACE gene were found to be significantly increased in patients with OSA as compared to patients without OSA. Frequency of II genotype was significantly decreased (OR = 0.46, 95 % CI 0.28–0.77, p?=?0.003) in OSA patients with hypertension. In contrast, the frequencies of ID (OR?=?1.80, 95 % CI 1.08–2.99, p?=?0.024) and DD genotypes (OR?=?2.15, 95 % CI 1.30–3.57, p?=?0.003) were significantly increased in this group. The activity of SACE was significantly decreased in the apneic group as compared to the non-apneic group (OR?=?0.99, 95 % CI 0.98–1.00, p?=?0.04).

Conclusions

The findings suggest that II genotype confers susceptibility towards development of OSA whereas DD genotype confers susceptibility towards hypertension irrespective of OSA.     

Genetic polymorphisms of ADH2 and ALDH2 association with esophageal cancer risk in southwest China

AIM＂ TO evaluate the impact of alcohol dehydrogenase 2 （ADH2） and aldehyde dehydrogenase 2 （ALDH2） polymorphisms on esophageal cancer risk. METHODS;One hundred and ninety-one esophageal cancer patients and 198 healthy controls from Yanting County were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase-chain-reaction with the confronting-two-pair-primer （PCR-CTPP） method. Unconditional logistic regression was used to calculate the odds ratios （OR） and 95% confidence interval （95% CI）. RESULTS; Both ADH2＊1 allele and ALDH2＊1/＊2 allele showed an increased risk of developing esophageal cancer. The adjusted OR （95% CI） for ADH2＊1 allele compared with ADH2＊2/＊2 was 1.65 （95% CI = 1.02-2.68） and 1.67 （95% CI = 1.02-2.72） for ALDH2＊1/＊2 compared with ALDH2＊1/＊1. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk, the OR was 1.83 （95% CI = 1.13-2.95）. Furthermore, when compared with ADH2＊2/＊2 and ALDH2＊1/＊1 carriers, ADH2＊1 and ALDH2＊2 carriers showed an elevated risk of developing esophageal cancer among non-alcohol drinkers     

Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus

OBJECTIVE: To assess the possible association between the PTPN22 gene 1858C-->T polymorphism and the predisposition and clinical expression of 2 systemic autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Our study population consisted of 826 RA patients, 338 SLE patients, and 1,036 healthy subjects. All subjects were of Spanish Caucasian origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. RESULTS: The overall distribution of genotypes in the RA patients was significantly different from that in the controls (P = 0.005, by chi-square test with 2 x 3 contingency tables). We observed a statistically significant difference in the distribution of the PTPN22 1858T allele between healthy subjects (7.4%), and RA patients (10.4%) (P = 0.001, odds ratio [OR] 1.45 [95% confidence interval (95% CI) 1.15-1.83]). In addition, PTPN22 1858 C/T and T/T genotypes were present at a significantly higher frequency in SLE patients than in controls (P = 0.02, OR 1.55 [95% CI 1.05-2.29]). Differences were also observed when allele frequencies were compared, with the PTPN22 1858T allele being present at a higher frequency among SLE patients (P = 0.03, OR 1.45 [95% CI 1.01-2.09]). CONCLUSION: These results suggest that the PTPN22 1858T allele may confer differential susceptibility to RA and SLE in the Spanish population.